The overall goal of this project is to investigate whether altered expression of histocompatibility antigens on tumor cells contributes significantly to immunological detection and eradication of nascent autochthonous lung tumors in mice. C3Hf mice differ from C3H/HeN mice and other mice of H-2Kk haplotype in an antigenic determinant coded for by the H-2K region of the major histocompatibility complex (MHC). At least two transplacentally induced lung tumors of C3Hf origin express an antigen cross reactive with, if not identical to, the H-2K coded antigen which distinguishes C3H mice from C3Hf mice. Administration of ethylnitrosourea (ENU) to adult mice induces highly malignant lung tumors in only certain mouse strains, e.g., A and BALB/c. Malignant lung tumors are not induced in genetically resistant mouse strains including C3H and C3Hf unless the carcinogen is administered transplacentally. Nevertheless, hyperplastic foci of type II pneumocytes (the cell type of lung tumor origin) are detectable in lungs of both genetically susceptible strain A and genetically resistant strain C3Hf adult mice 4 to 8 weeks after ENU administration. This project will test the hypothesis that an immunological mechanism is responsible for regression of hyperplastic foci induced in adult C3Hf and C3H mice and will test whether the antigen responsible for immune surveillance is coded for by the H-2K region of the MHC. Hyperplastic and neoplastic cells will also be examined for I-A coded MHC antigens. Antitumor immune responses in ENU-treated mice will be characterized, and the relative contributions of T cell-dependent and T cell-independent effector mechanisms will be assessed. Furthermore, tumor induction in immunologically impaired animals will be compared with that in normal mice, and the effects of specific pre-immunization on tumor induction will be determined. These studies will directly address the concept of immune surveillance of lung tumors in adult C3Hf and C3H mice and may indicate how altered expression of MHC-coded antigens on tumor cells determines the specificity and the nature of antitumor immunity. This project will provide necessary groundwork for specific studies correlating genetically determined differences in spontaneous lung tumor development with genetically controlled differences in capacity to modify expression of MHC-coded antigens.